Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands.

Autor: Stunnenberg BC; Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Bas.Stunnenberg@radboudumc.nl., Raaphorst J; Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands., Deenen JCW; Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands., Links TP; Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Wilde AA; Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Medical Centre, Amsterdam, The Netherlands., Verbove DJ; Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands., Kamsteeg EJ; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., van den Wijngaard A; Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Faber CG; Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands., van der Wilt GJ; Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands., van Engelen BGM; Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands., Drost G; Department of Neurology and Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Ginjaar HB; Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2018 May; Vol. 28 (5), pp. 402-407. Date of Electronic Publication: 2018 Mar 09.
DOI: 10.1016/j.nmd.2018.03.006
Abstrakt: Few reliable data exist on the prevalence of skeletal muscle channelopathies. We determined the minimum point prevalence of genetically-defined skeletal muscle channelopathies in the Netherlands and report their mutation spectrum. Minimum point prevalence rates were calculated as number of genetically-confirmed skeletal muscle channelopathy patients (CLCN1, SCN4A, CACNA1S and KCNJ2 gene mutations) in the Netherlands (1990-2015) divided by the total number of at-risk individuals. Rates were expressed as cases/100.000 and 95% confidence intervals were calculated based on Poisson distribution. Results of standardized genetic diagnostic procedures were used to analyze mutation spectra. We identified 405 patients from 234 unrelated pedigrees, resulting in a minimum point prevalence of 2.38/100.000 (95% CI 2.16-2.63) for skeletal muscle channelopathies in the Netherlands. Minimum point prevalence rates for the disease groups, non-dystrophic myotonia and periodic paralysis, were 1.70/100.000 and 0.69/100.000 respectively. Sixty-one different CLCN1 mutations (including 12 novel mutations) were detected in myotonia congenita. Twenty-eight different SCN4A missense mutations (including three novel mutations) were identified in paramyotonia congenita/sodium channel myotonia, hypokalemic periodic paralysis and hyperkalemic periodic paralysis. Four different CACNA1S missense mutations were detected in hypokalemic periodic paralysis and five KCNJ2 missense mutations in Andersen-Tawil syndrome. The minimum point prevalence rates for genetically-defined skeletal muscle channelopathies confirm their rare disease status in the Netherlands. Rates are almost twice as high as in the UK and more in line with pre-genetic prevalence estimates in parts of Scandinavia. Future diagnostic and therapeutic studies may benefit from knowledge of the mutation spectrum of skeletal muscle channelopathies.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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